Genetic predisposition influences disease course

The ratio of interleukin-1 to its antagonist determines the individual immune response to bacterial infection in the periodontium. The delicate balance is genetically determined and thus has a decisive influence on the inflammatory response.

Immune response is triggered by interleukin-1

If the cells of the junctional epithelium, especially macrophages, come into contact with antigens, such as cell wall components of periodontopathogenic bacteria, this can lead to increased release of interleukins. These trigger the inflammatory and immune response and are thus involved in combating bacterial pathogens. Interleukin-1 (IL-1) also plays an important role in regulating bone metabolism. It stimulates bone resorption by inducing the differentiation of osteoclast precursor cells and at the same time inhibits osteoblasts.

Interplay of interleukin-1 and receptor antagonist

If IL-1 is released, it binds to its receptor, which is present on the surface of various target cells. This specific binding leads to activation, which initiates further inflammatory and immune responses. The natural inhibitor of IL-1 is the IL-1 receptor antagonist (IL-1RN). This binds to the same receptor, but blocks it rather than activating it. When the stimulus subsides, IL-1RN thus brings about a gradual reduction in the immune and inflammatory responses. If the interaction between IL-1 and IL-1RN is impaired as a result of genetic variations, the affected patient tends to have increased inflammatory responses to external stimuli.

Polymorphism in the interleukin-1 receptor antagonist gene

If an IL-1 receptor antagonist gene variant is present, the binding of IL-1 to the IL-1 receptor can no longer be blocked sufficiently. This leads to weakened inhibition of inflammatory processes, as the transmission of the inflammatory signal is not terminated.

Combination of polymorphisms

If IL-1 overproduction occurs because of variations in the IL-1A and IL-1B genes at the same time as weakened inhibition of inflammation caused by variation in the IL-1RN gene, this results in the patient having a greatly increased tendency to inflammation. The low IL-1RN concentrations cannot compensate for the excessive presence of IL-1, which further increases the inflammatory effect of the IL-1. Such patients are therefore extremely sensitive to periodontopathogenic bacteria and other external stimuli. They are at increased risk of early disease onset and a severe disease course.